In most animal systems, carbon monoxide is a waste product produced in the breakdown of free hemoglobin within the blood. Ordinarily, hemoglobin is contained within red blood cells and is stable. However, aging of red blood cells and certain disease processes produce hemolysis, i.e., the breakdown of the cell wall. This produces free hemoglobin which breaks down in the blood. The carbon monoxide that is produced by the breakdown of free hemoglobin is normally excreted in the breath.
When the system is in equilibrium, the carbon monoxide concentration in the breath is proportional to the difference in the concentration of carbon monoxide in the blood and the concentration of carbon monoxide in room air. This difference in concentration is proportional to the rate of hemolysis in the blood.
The concentration of carbon monoxide in the end-tidal breath, i.e., the gas that is last expelled each breath, is presumed to be at equilibrium with the concentration in the blood. This is because the end-tidal breath contains predominantly, if not exclusively, the gas expelled from the alveoli in the lungs, which gas was within the alveoli for a time generally sufficient to equilibrate with the blood.
It is known that hemolysis and the resulting byproducts and consequences of hemolysis can be estimated or predicted from a measure of the concentration of carbon monoxide in the end-tidal breath. See Smith, D. W. et al., "Neonatal Bilirubin Production Estimated from End-Tidal Carbon Monoxide Concentration", Journal of Pediatric Gastroenterology and Nutrition, 3:77-80, 1984.
One method of analysis previously reported includes incrementally acquiring a sample of end-tidal breath and analyzing the acquired sample by mass spectroscopy or gas chromatography to determine the end-tidal carbon monoxide concentration. The sample is obtained by extracting from each of several successive breaths a portion of the apparent end-tidal breath using a syringe. The end-tidal portion of breath is determined by observing the chest movements of the infant. See, e.g., Vreman et al. U.S. Pat. No. 4,831,024.
One problem with this technique is that it requires a skilled, trained user to obtain the end-tidal sample in successive increments based on watching chest wall movements. It also requires a trained, skilled person to operate a complex piece of analytical laboratory equipment to analyze the acquired sample. In addition, this technique requires time and personnel to transport the sample from the patient to the laboratory (or equipment) where the analysis is conducted, and then to report back to the attending physician/practitioner for a diagnosis and prescription, if any.
Another problem with this technique is that accurate assessment of the concentration difference in carbon monoxide requires obtaining good samples of end-tidal patient breath. This essentially requires that the patient have a regular, predictable breathing cycle. Thus, it can be difficult to obtain a good sample by watching chest wall movement, particularly for a newborn and for patients having irregular breathing cycles.
Chemical electrochemical sensors capable of measuring carbon monoxide concentrations in the range of interest, 0 to 500 parts per million (ppm), are commercially available, e.g., model DragerSensor CO available from Dragerwerk, Lubeck, Germany. However, such sensors are sensitive to many other gases as well as carbon monoxide, and are therefore susceptible to error. Another problem with such sensors is that the measurement dynamics of the sample gas transport through the gas permeable membrane and oxidation-reduction in the electrochemical cell results in a relatively slow response time such that discrete samples of the end-tidal breath must be obtained and analyzed to determine the end-tidal carbon monoxide concentration.